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In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence.

Publication ,  Journal Article
Madonna, MC; Duer, JE; McKinney, BJ; Sunassee, ED; Crouch, BT; Ilkayeva, O; Hirschey, MD; Alvarez, JV; Ramanujam, N
Published in: NPJ Breast Cancer
September 26, 2022

Recurrent cancer cells that evade therapy is a leading cause of death in breast cancer patients. This risk is high for women showing an overexpression of human epidermal growth factor receptor 2 (Her2). Cells that persist can rely on different substrates for energy production relative to their primary tumor counterpart. Here, we characterize metabolic reprogramming related to tumor dormancy and recurrence in a doxycycline-induced Her2+/Neu model of breast cancer with varying times to recurrence using longitudinal fluorescence microscopy. Glucose uptake (2-NBDG) and mitochondrial membrane potential (TMRE) imaging metabolically phenotype mammary tumors as they transition to regression, dormancy, and recurrence. "Fast-recurrence" tumors (time to recurrence ~55 days), transition from glycolysis to mitochondrial metabolism during regression and this persists upon recurrence. "Slow-recurrence" tumors (time to recurrence ~100 days) rely on both glycolysis and mitochondrial metabolism during recurrence. The increase in mitochondrial activity in fast-recurrence tumors is attributed to a switch from glucose to fatty acids as the primary energy source for mitochondrial metabolism. Consequently, when fast-recurrence tumors receive treatment with a fatty acid inhibitor, Etomoxir, tumors report an increase in glucose uptake and lipid synthesis during regression. Treatment with Etomoxir ultimately prolongs survival. We show that metabolic reprogramming reports on tumor recurrence characteristics, particularly at time points that are essential for actionable targets. The temporal characteristics of metabolic reprogramming will be critical in determining the use of an appropriate timing for potential therapies; namely, the notion that metabolic-targeted inhibition during regression reports long-term therapeutic benefit.

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Published In

NPJ Breast Cancer

DOI

ISSN

2374-4677

Publication Date

September 26, 2022

Volume

8

Issue

1

Start / End Page

111

Location

United States

Related Subject Headings

  • 4202 Epidemiology
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Madonna, M. C., Duer, J. E., McKinney, B. J., Sunassee, E. D., Crouch, B. T., Ilkayeva, O., … Ramanujam, N. (2022). In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence. NPJ Breast Cancer, 8(1), 111. https://doi.org/10.1038/s41523-022-00481-3
Madonna, Megan C., Joy E. Duer, Brock J. McKinney, Enakshi D. Sunassee, Brian T. Crouch, Olga Ilkayeva, Matthew D. Hirschey, James V. Alvarez, and Nirmala Ramanujam. “In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence.NPJ Breast Cancer 8, no. 1 (September 26, 2022): 111. https://doi.org/10.1038/s41523-022-00481-3.
Madonna MC, Duer JE, McKinney BJ, Sunassee ED, Crouch BT, Ilkayeva O, et al. In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence. NPJ Breast Cancer. 2022 Sep 26;8(1):111.
Madonna, Megan C., et al. “In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence.NPJ Breast Cancer, vol. 8, no. 1, Sept. 2022, p. 111. Pubmed, doi:10.1038/s41523-022-00481-3.
Madonna MC, Duer JE, McKinney BJ, Sunassee ED, Crouch BT, Ilkayeva O, Hirschey MD, Alvarez JV, Ramanujam N. In vivo metabolic imaging identifies lipid vulnerability in a preclinical model of Her2+/Neu breast cancer residual disease and recurrence. NPJ Breast Cancer. 2022 Sep 26;8(1):111.

Published In

NPJ Breast Cancer

DOI

ISSN

2374-4677

Publication Date

September 26, 2022

Volume

8

Issue

1

Start / End Page

111

Location

United States

Related Subject Headings

  • 4202 Epidemiology
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences